A Factor IX Gene Therapy Study (FIX-GT) (FIX-GT)
Hemophilia B
About this trial
This is an interventional treatment trial for Hemophilia B
Eligibility Criteria
Inclusion Criteria:
- Adults males, ≥ 18 years of age;
Confirmed diagnosis of HB defined as one of the following:
Documented severe FIX deficiency with plasma FIX activity of <1% of normal or moderately severe FIX deficiency with plasma FIX activity level between ≥1% and ≤2% and a severe bleeding phenotype defined by one of the following:
- On prophylaxis for a history of bleeding, or
- On-demand therapy with a current or past history of 4 or more bleeding episodes/year, or
- Evidence of chronic haemophilic arthropathy (pain, joint destruction, and loss of range of motion).
- Able to give full informed consent and able to comply with all requirements of the trial including 15-year long-term follow-up;
- Willing to practice barrier contraception until at least two consecutive semen samples after vector administration are negative for vector sequences;
- Lack of neutralising anti-AAV antibodies using an in-vivo transduction inhibition assay;
- At least 150 exposure days to FIX concentrates.
Exclusion Criteria:
- Presence of neutralising anti-human FIX antibodies (inhibitor, determined by the Bethesda inhibitor assay) at the time of enrolment or a previous history of FIX inhibitor;
- Patients at high risk of thromboembolic events (high risk patients would include those with a history of arterial or venous thromboembolism (e.g. deep vein thrombosis, pulmonary embolism, non-haemorrhagic stroke, arterial embolus) and those with acquired thrombophilia including conditions such as atrial fibrilation);
- Use of investigational therapy for haemophilia within 30 days before enrolment;
- Patients with active hepatitis B or C, and HBsAg or HCV RNA viral load positivity, respectively, or currently on antiviral therapy for hepatitis B or C. Negative viral assays in 2 samples, collected at least 6 months apart, will be required to be considered negative. Both natural clearers and those who have cleared HCV on antiviral therapy are eligible.;
- Serological evidence of HIV-1;
- Evidence of liver dysfunction (persistently elevated alanine aminotransaminase, aspartate aminotransferase, bilirubin >1.5 x upper limit of normal);
- Platelet count <50 x 109/L;
- Uncontrolled glaucoma, diabetes mellitus, or hypertension;
- Malignancy requiring treatment;
- Patients with uncontrolled cardiac failure, unstable angina or myocardial infarction in the past 6 months;
- Poor performance status (World Health Organization score >1);
- Prior treatment with any gene transfer medicinal product;
- Known or suspected intolerance, hypersensitivity or contraindication to the investigational product and non-investigational medicinal products or their excipients;
- Planned major elective surgery prior to the end of trial.
- Current or relavant history of a physical or psychiatric illness or any medical condition that in the opinion of the investigator could affect the patients safety or interfere with the study assessments.
- CMV IgG postive patients who are CMV PCR positive at screening.
Sites / Locations
- St Jude Children's Research Hospital
- St James's Hospital
- University of Milan
- Basingstoke Haemostasis and Thrombosis Centre
- East Kent Hospitals University
- Guy's and St Thomas's NHS Foundation Trust
- Royal Free Hospital
- Newcastle Hospitals NHS Trust
- Oxford University Hospital
- University of Sheffield
- University Hospital Southampton
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
FLT180a, 6x10e^11 vg/kg solution for infusion
FLT180a, 2 x 10e^12 vg/kg solution for infusion
FLT180a, 1x10e^12 vg/kg solution for infusion
FLT180a, 1.3x10e^12 vg/kg solution for infusion
Participants receiving gene therapy vector at a dose of 6x10e^11 vg/kg
Participants receiving gene therapy vector at a dose of 2 x 10e^12 vg/kg
Participants receiving gene therapy vector at a dose of 1 x 10e^12 vg/kg
Participants receiving gene therapy vector at a dose of 1.3 x 10e^12 vg/kg